International Registry on Cholangiocarcinoma Treatment (CHOLANGIO)

Cholangiocarcinoma is a rare and very aggressive neoplasm that arises from the biliary epithelium, constitutes approximately 2% of all reported cancer, and accounts for about 3% of all gastrointestinal malignancies. Up to date, there are many modalities to diagnosis and treat with a range of sensitivity and specificity, and also the advantage and disadvantage of its modality. Cholangiocarcinoma has a poor prognosis. Surgical resection offers the only curative option and usually requires a major hepatic resection in addition to resection of the cholangiocarcinoma. Unfortunately, curative resection is possible in only about 30% of patients due to locally advanced disease, distant metastases or comorbidity in elderly patients. Even after resection, the recurrence rate is approximately 60%, resulting in a low 5-year overall survival (OS).

Patients with intra-hepatic Cholangiocarcinoma (ICC) have a very limited benefit from systemic chemotherapy, indeed, in unresectable cholangiocarcinoma Overall Survival with systemic chemotherapy is less than 1 year. Since most cholangiocarcinoma patients develop distant metastases at late stages only, locoregional therapy is an interesting therapeutic strategy.

Locoregional therapy studies in patients with intrahepatic cholangiocarcinoma employing radiofrequency ablation (RFA), transarterial chemoembolization (TACE) or external as well as internal radiation therapy yielded promising results in the last couple of years.

TACE is safe and may be effective for prolonging the survival of patients with nonresectable combined hepatocellular carcinoma (HCC) -cholangiocarcinoma, as compared with the historically reported survivals of these patients. Tumor vascularity is highly associated with tumor response. The patient survival period after TACE for combined HCC-cholangiocarcinoma is significantly dependent on tumor size, tumor vascularity, Child-Pugh class, and presence or absence of portal vein invasion.

Currently, few centers perform TACE therapy for unresectable Cholangiocarcinoma. Several European studies have reported the efficacy and safety TACE for ICC.

The establishment of a registry to obtain the majority of Cholangiocarcinoma cases treated with locoregional approach within and outside Europe can help the investigators evaluate a larger and non-ambiguous sample population. This would help the investigators evaluate the technical success rates, clinical success rates, feasibility and safety of TACE for ICC.

Study Overview

• Status: Unknown
• Conditions: Cholangiocarcinoma
• Intervention / Treatment: Drug: Doxorubicin

Detailed Description

Study Design: Prospective observational study

Primary objective: This is a data collection study where the main purpose is to collect information about the treatments that patients receive for their unresectable cholangiocarcinoma.

Secondary objectives: To create an international Registry including patients undergoing locoregional treatments, to correlate tumour characteristics with outcome, survival and prognosis; to identify criteria for guiding therapy including TACE, chemoinfusion and other locoregional treatments

Treatment modalities for TACE

Day -1 Doxorubicina 50-75 mg/mq has been charged onto 2 ml of 70-150 µm M1 microspheres at Pharmacy.

Day -1 : prehydration, antibiotic prophylaxis and setting up of a therapeutic scheme appropriate for analgesic prophylaxis (3-day duration) as previously reported 1 vial of tropisetron (diluted in 100ml of physiological solution) administered by slow drip Day 0: Upon admittance to the radiology room, the patient receive morphine hydrochloride 10 mgr diluted in 100 ml of salin solution i.v. (to be repeated one hour after the procedure and if necessary also after 6 hours).

Tropisetron i.v. if needed. Intra-arterial premedication with 2.5 mgr of verapamil 2.5 mgr diluted in 4 ml of normal saline solution followed by 4 ml of lidocaine 2%.

Selected arterial Infusion (considering tumor uptake and dominant disease) of doxorubicina 50-75 mg preloaded into 2 ml of 70-150 µm M1 microspheres.

Second infusion of doxorubicin at the same dose into 2 ml of 70-150 µm M1 microspheres can be administered in a further TACE (oncologist's planning of cure).

Day +30: The above procedure is repeated. Day +90: In case of response, a third administration following the above procedures will be repeated

Evaluation of response

Response must be assessed by repeating the following examinations at Day 30, Day 90 and Day 120 after start of treatment:

Chest-abdomen CAT scan with and without contrast medium (refer to Section 4). Evaluation will be based on the Response Evaluation Criteria In Solid Tumors (RECIST) cancer markers (CEA), Cancer Antigen (CA) 19.9)

Assessment of quality of life The Edmonton Symptom Assessment System (ESAS) is used to monitor health conditions and quality of life.

The questionnaire must be filled in by the patient unaided by family members or by health care personnel, over a period of about 15 minutes. Assessment of quality of life will be performed during the baseline visit and at Day 30, Day 60 and Day 120 from start of treatment.

• Study Type: Observational
• Enrollment (Anticipated): 40

Contacts and Locations

Study Locations

• Italy
  • Pesaro, Italy, 61122
    • Recruiting
    • Azienda Ospedaliera Ospedali Riuniti Marche Nord, Presidio Ospedaliero San Salvatore
    • Principal Investigator: Giammaria Fiorentini, MD
    • Contact: Giammaria Fiorentini, MD; Phone Number: 4124 +39072136; Email: giammaria.fiorentini@ospedalimarchenord.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

primary care clinic

Description

Inclusion Criteria:

1. The diagnosis of cholangiocarcinoma will be established preoperatively by at least one of the following criteria: a) positive brush cytology or biopsy result obtained at the time of cholangiography; b) Fluorescence in situ hybridization demonstrating aneuploidy; c) serum CA 19-9 value greater than 100 U/mL in the presence of a radiographically characteristic malignant stricture in the absence of cholangitis.
2. Tumor is above the cystic duct and is unresectable.
3. Patient is a suitable candidate for the study by a radiation oncologist, a medical oncologist, and the liver surgeon
4. Maximum Eastern Cooperative Oncology Group performance status of 2 and a minimum daily caloric intake of 1200kcal.
5. No evidence of metastatic disease.
6. Between ages 18 - 75.
7. Patient must provide written informed consent.

Exclusion Criteria:

1. Patients with intrahepatic metastasis presenting liver involvement more than 75%
2. Patients with uncontrolled infections (sepsis)
3. Evidence of extrahepatic disease, including local lymph node metastasis (except peri-hilar nodes).
4. History of another malignancy diagnosed within 5 years, excluding "in situ" skin and cervical cancers, without metastases.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

doxorubicin; Day +1: Lobar Infusion ( lobe with dominant disease) of Doxorubicin preloaded into 2 ml of 70-150 µm M1 microspheres. Second lobar infusion of Doxorubicin preloaded into 2 ml of 70-150 µm M1 microspheres can be administered at the same time contralaterally or in a further TACE Day +30: The above procedure is repeated. Day +90: In case of response, a third administration following the above procedures will be repeated

Drug: Doxorubicin; Doxorubicina is loaded at the concentration of 50-75 mg/mq onto 2 ml of 70-150 µm M1 microspheres and is infused by TACE method; Other Names: Adriamycin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
tumor response	CT scan evaluated with RECIST 1.1	12 months
overall survival	survival from start of treatment	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
number adverse events	number of adverse events observed for each patient	4 months

Collaborators and Investigators

• Sponsor: International Group of Endovascular Oncology
• Investigators: Principal Investigator: Giammaria Fiorentini, MD, International Group of Endovascular Oncology

Publications and helpful links

General Publications

• Aliberti C, Benea G, Tilli M, Fiorentini G. Chemoembolization (TACE) of unresectable intrahepatic cholangiocarcinoma with slow-release doxorubicin-eluting beads: preliminary results. Cardiovasc Intervent Radiol. 2008 Sep-Oct;31(5):883-8. doi: 10.1007/s00270-008-9336-2. Epub 2008 May 14.
• Cantore M, Fiorentini G, Mambrini A, Rabbi C, Zamagni D, Carlone N, Manni A, Caudana R, Torri T. Regional combined with systemic chemotherapy in unresectable biliary tract cancers: a phase II study. J Exp Clin Cancer Res. 2003 Dec;22(4 Suppl):59-64.
• Fiorentini G, Mambrini A, Sarti D, Cantore M, Mulazzani L, Mattioli GM, Guadagni S. Hepatic intra-arterial and systemic chemotherapy followed by maintenance therapy for the treatment of cholangiocarcinoma. Hepat Oncol. 2017 Apr;4(2):45-53. doi: 10.2217/hep-2017-0001. Epub 2017 Aug 31.

Helpful Links

• International group of endovascular oncology (IGEVO) website

Study record dates

Study Major Dates

• Study Start: July 1, 2013
• Primary Completion (Anticipated): July 1, 2019
• Study Completion (Anticipated): August 1, 2020

Study Registration Dates

• First Submitted: August 7, 2013
• First Submitted That Met QC Criteria: August 8, 2013
• First Posted (Estimate): August 12, 2013

Study Record Updates

• Last Update Posted (Actual): February 27, 2019
• Last Update Submitted That Met QC Criteria: February 26, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: cholangiocarcinoma; doxorubicin; transarterial chemoembolization; tumor response
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Cholangiocarcinoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Doxorubicin
• Other Study ID Numbers: CHOLANGIO01; CHOLANGIO100513 (Other Identifier: IGEVO)